Amblyopia is the most significant disorder of spatial vision in children. Since spatial vision develops during a postnatal critical period, amblyopia must be detected early and targeted by effective therapeutic interventions. There is a broad appreciation for the anatomic and physiologic consequences that monocular deprivation, the accepted experimental model for amblyopia, has at the level of the lateral geniculate relay nucleus and primary visual cortex. However, the relative lack of knowledge of the molecular alterations produced at these sites is a severe hindrance to development of both better disease models and pharmacologic interventions for amblyopia. Here, we propose to conduct pilot studies that will address this important gap in understanding amblyopia. Using genome-wide expression profiling and contemporary bioinformatics tools in monkeys reared with amblyopia, we will determine the broad molecular alterations that monocular deprivation produces in the thalamus and primary visual cortex. This proposal meets the criteria of innovative and high impact research required for the NEI Small Grants for Pilot Research Program (R03), because it is among the first to address amblyopia's fundamental molecular consequences. Our overall hypothesis is that the magnocellular and parvocellular visual relay pathways are molecularly distinct from each other and exhibit differential responses to amblyopia which will be determined by genome-wide expression profiling. Our specific objectives are to (a) dissect the normal gene expression signatures of the magnocellular and parvocellular pathways at the level of the lateral geniculate nucleus and primary visual cortex (Specific Aim 1) and (b) identify patterned gene expression changes induced by monocular deprivation in the lateral geniculate nucleus and primary visual cortex (V1), with emphasis upon differential responses of the parvocellular and magnocellular zones (Specific Aim 2). To accomplish these goals we will combine the technologies of laser microdissection, DNA microarray, and bioinformatics to broadly profile gene expression patterns in the lateral geniculate nucleus and primary visual cortex of normally reared and monocularly deprived monkeys, the most accepted model of amblyopia. The health-relatedness of this proposal is that our data will yield important new insights into the molecular mechanisms of amblyopia that will contribute toward the design of new treatment regimens. [unreadable] [unreadable]